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Clinical outcomes to pemetrexed-based versus non-pemetrexed-based platinum doublets in patients with KRAS-mutant advanced non-squamous non-small cell lung cancer.
Ricciuti, B; Brambilla, M; Cortellini, A; De Giglio, A; Ficorella, C; Sidoni, A; Bellezza, G; Crinò, L; Ludovini, V; Baglivo, S; Metro, G; Chiari, R.
Afiliación
  • Ricciuti B; Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, University of Perugia, via Dottori, 1, 06156, Perugia, Italy. biagio.ricciuti@gmail.com.
  • Brambilla M; Medical Oncology Department, Fondazione IRCCS Istituto Nazionale per lo Studio e la Cura dei Tumori, University of Milan, Milan, Italy.
  • Cortellini A; Medical Oncology, Department of Biotechnological and Applied Clinical Sciences, St. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy.
  • De Giglio A; Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, University of Perugia, via Dottori, 1, 06156, Perugia, Italy.
  • Ficorella C; Medical Oncology, Department of Biotechnological and Applied Clinical Sciences, St. Salvatore Hospital, University of L'Aquila, L'Aquila, Italy.
  • Sidoni A; Division of Pathology and Histology, Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy.
  • Bellezza G; Division of Pathology and Histology, Department of Experimental Medicine, University of Perugia Medical School, Perugia, Italy.
  • Crinò L; Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy.
  • Ludovini V; Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, University of Perugia, via Dottori, 1, 06156, Perugia, Italy.
  • Baglivo S; Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, University of Perugia, via Dottori, 1, 06156, Perugia, Italy.
  • Metro G; Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, University of Perugia, via Dottori, 1, 06156, Perugia, Italy.
  • Chiari R; Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, University of Perugia, via Dottori, 1, 06156, Perugia, Italy.
Clin Transl Oncol ; 22(5): 708-716, 2020 May.
Article en En | MEDLINE | ID: mdl-31332704
PURPOSE: KRAS mutation has been associated with enhanced dependency on the folate metabolism in preclinical studies. However, whether KRAS mutation correlates to increased sensitivity to pemetrexed in patients with advanced NSCLC is unknown. METHODS: Patients with advanced non-squamous NSCLC who had a documented EGFR and ALK WT genotype with simultaneous KRAS mutation assessment were evaluated for clinical outcome to pemetrexed- and non-pemetrexed-based first-line platinum doublet according to KRAS mutation status. RESULTS: Of 356 patients identified, 138 harbored a KRAS mutation. Among KRAS-mutant NSCLCs, those treated with platinum/pemetrexed (81/138) had significantly lower ORR (30.9% versus 47.4%, P = 0.05), DCR (51.8% versus 71.9%, P = 0.02) and shorter median progression-free survival [mPFS 4.1 versus 7.1 months, HR 1.48 (95% CI 1.03-2.12), P = 0.03] and median overall survival [mOS 9.7 versus 26.9 months, HR 1.93 (95% CI 1.27-2.94), P = 0.002] compared to those who received a non-pemetrexed-based platinum doublet (57/138). No difference in ORR, DCR, mPFS and mOS was observed between KRAS WT patients who received a pemetrexed-based (124/218) versus non-pemetrexed base platinum doublets (94/218). After adjusting for performance status, age and the presence of brain metastasis at baseline, treatment with pemetrexed-based platinum doublet was associated with an increased risk of death [HR 2.27 (95% CI 1.12-4.63), P = 0.02] among KRAS-mutant patients in multivariate analysis. CONCLUSION: Patients with KRAS-mutant lung adenocarcinoma have a poorer outcome on pemetrexed-based first-line chemotherapy. Whether KRAS-mutant NSCLCs should be excluded from pemetrexed-containing regimens should be assessed prospectively.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Proteínas Proto-Oncogénicas p21(ras) / Carcinoma de Pulmón de Células no Pequeñas / Pemetrexed / Neoplasias Pulmonares Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Transl Oncol Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Italia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Protocolos de Quimioterapia Combinada Antineoplásica / Proteínas Proto-Oncogénicas p21(ras) / Carcinoma de Pulmón de Células no Pequeñas / Pemetrexed / Neoplasias Pulmonares Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Transl Oncol Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Italia